Electronic pacemakers are lifesaving devices that provide a regular heartbeat in settings where the sinoatrial node, atrioventricular conduction, or both, have failed. Thus, one of the major indications for electronic pacemaker therapy is high degree heart block, such that a normally functioning sinus node impulse cannot propagate to the ventricle. The result is ventricular arrest and/or fibrillation, and death.
Malfunction or loss of pacemaker cells can occur due to disease or aging. For example, acute myocardial infarction (MI) kills millions of people each year and generally induces in survivors marked reductions in myocyte number and cardiac pump function. Adult cardiac myocytes divide only rarely, and the usual responses to myocyte cell loss include compensatory hypertrophy and/or congestive heart failure, a disease with a significant annual mortality. There have been recent reports of the delivery of bone marrow-derived and/or circulating human mesenchymal stem cells (hMSCs) to the hearts of post-myocardial infarct patients resulting in some improvement of mechanical performance (Strauer et al., 2002; Perin et al., 2003) in the absence of overt toxicity. The presumption in these and other animal studies (Orlic et al., 2001) is that the hMSCs integrate into the cardiac syncytium and then differentiate into new heart cells restoring mechanical function.
An alternative application of cell therapy, described herein, involves growing cells such as hMSCs into a bypass bridge comprising a tract of gap junction-coupled cells that can be used to conduct pacemaker and/or electrical current/signals across a region of the heart exhibiting impaired electrical conduction.